US Assessment of HPV Types in Cancers: Implications for Current and 9-Valent HPV Vaccines

Background Human papillomavirus (HPV) infection, particularly with type 16, causes a growing fraction of oropharyngeal cancers, whose incidence is increasing, mainly in developed countries. In a double-blind controlled trial conducted to investigate vaccine efficacy (VE) of the bivalent HPV 16/18 vaccine against cervical infections and lesions, we estimated VE against prevalent oral HPV infections 4 years after vaccination. Methods and Findings A total of 7,466 women 18–25 years old were randomized (1∶1) to receive the HPV16/18 vaccine or hepatitis A vaccine as control. At the final blinded 4-year study visit, 5,840 participants provided oral specimens (91·9% of eligible women) to evaluate VE against oral infections. Our primary analysis evaluated prevalent oral HPV infection among all vaccinated women with oral and cervical HPV results. Corresponding VE against prevalent cervical HPV16/18 infection was calculated for comparison. Oral prevalence of identifiable mucosal HPV was relatively low (1·7%). Approximately four years after vaccination, there were 15 prevalent HPV16/18 infections in the control group and one in the vaccine group, for an estimated VE of 93·3% (95% CI = 63% to 100%). Corresponding efficacy against prevalent cervical HPV16/18 infection for the same cohort at the same visit was 72·0% (95% CI = 63% to 79%) (p versus oral VE = 0·04). There was no statistically significant protection against other oral HPV infections, though power was limited for these analyses. Conclusions HPV prevalence four years after vaccination with the ASO4-adjuvanted HPV16/18 vaccine was much lower among women in the vaccine arm compared to the control arm, suggesting that the vaccine affords strong protection against oral HPV16/18 infection, with potentially important implications for prevention of increasingly common HPV-associated oropharyngeal cancer. ClinicalTrials.gov, Registry number NCT00128661

Type-specific prevalence data of human papillomavirus (HPV) DNA in penile carcinoma are needed to determine the potential impact of HPV prophylactic vaccines, assuming demonstrated efficacy in men. A review was conducted using search terms including HPV and penile cancer. Studies using polymerase chain reaction (PCR) assays for HPV DNA detection in invasive penile carcinoma were included. A total of 1,266 squamous cell carcinoma (SCC) cases contributed data from 30 studies. The number of SCC was similar in Europe (28.2%), North America (27.6%), South America (23.9%) and Asia (20.4%). All SCC were histologically confirmed with biopsies for DNA detection. Most commonly used PCR primers were type-specific (35.2%), and combination PCR (18.2%). HPV prevalence was 47.9%, ranging from 22.4% in verrucous SCC to 66.3% for the basaloid/warty subtypes. HPV16 (30.8%), HPV6 (6.7%) and HPV18 (6.6%) were the most prevalent types. HPV16 and/or HPV 18 prevalence was 36.7%. HPV DNA was detected in half of SCC, with HPV16 being the most common type. If proven efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and 18 could potentially reduce approximately one-third of incident SCC.

Background Australia was one of the first countries to introduce a publicly funded national human papillomavirus (HPV) vaccination program that commenced in April 2007, using the quadrivalent HPV vaccine targeting 12- to 13-year-old girls on an ongoing basis. Two-year catch-up programs were offered to 14- to 17- year-old girls in schools and 18- to 26-year-old women in community-based settings. We present data from the school-based program on population-level vaccine effectiveness against cervical abnormalities in Victoria, Australia. Methods Data for women age-eligible for the HPV vaccination program were linked between the Victorian Cervical Cytology Registry and the National HPV Vaccination Program Register to create a cohort of screening women who were either vaccinated or unvaccinated. Entry into the cohort was 1 April 2007 or at first Pap test for women not already screening. Vaccine effectiveness (VE) and hazard ratios (HR) for cervical abnormalities by vaccination status between 1 April 2007 and 31 December 2011 were calculated using proportional hazards regression. Results The study included 14,085 unvaccinated and 24,871 vaccinated women attending screening who were eligible for vaccination at school, 85.0% of whom had received three doses. Detection rates of histologically confirmed high-grade (HG) cervical abnormalities and high-grade cytology (HGC) were significantly lower for vaccinated women (any dose) (HG 4.8 per 1,000 person-years, HGC 11.9 per 1,000 person-years) compared with unvaccinated women (HG 6.4 per 1,000 person-years, HGC 15.3 per 1,000 person-years) HR 0.72 (95% CI 0.58 to 0.91) and HR 0.75 (95% CI 0.65 to 0.87), respectively. The HR for low-grade (LG) cytological abnormalities was 0.76 (95% CI 0.72 to 0.80). VE adjusted a priori for age at first screening, socioeconomic status and remoteness index, for women who were completely vaccinated, was greatest for CIN3+/AIS at 47.5% (95% CI 22.7 to 64.4) and 36.4% (95% CI 9.8 to 55.1) for women who received any dose of vaccine, and was negatively associated with age. For women who received only one or two doses of vaccine, HRs for HG histology were not significantly different from 1.0, although the number of outcomes was small. Conclusion A population-based HPV vaccination program in schools significantly reduced cervical abnormalities for vaccinated women within five years of implementation, with the greatest vaccine effectiveness observed for the youngest women.